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| Mendeliome v1.3225 | MT-TW |
Zornitza Stark gene: MT-TW was added gene: MT-TW was added to Mendeliome. Sources: Expert list mtDNA tags were added to gene: MT-TW. Mode of inheritance for gene gene: MT-TW was set to MITOCHONDRIAL Publications for gene: MT-TW were set to 7695240; 9266739; 9673981; 12776230; 15054399; 18337306; 19809478; 26524491; 23841600; 30937556 Phenotypes for gene: MT-TW were set to Mitochondrial disease (MONDO:0044970), MT-TW-related Review for gene: MT-TW was set to GREEN Added comment: DEFINITIVE by ClinGen. At least 10 individuals reported. Age of onset in affected individuals ranged from childhood to adulthood. Clinical features in affected individuals included LSS, microcephaly, developmental delay and regression, cognitive decline, fatigue, seizures, ataxia, chorea, muscle wasting, axonal neuropathy, diabetes, liver steatosis and fibrosis, constipation, recurrent vomiting, failure to thrive, pigmentary retinopathy, ptosis, optic atrophy, ophthalmoplegia, sensorineural hearing loss, and hypertrophic and dilated cardiomyopathy. Brain imaging was variable and ranged from normal to findings consistent with LSS to generalized atrophy and white matter involvement. Muscle biopsies showed ragged red fibers, COX-deficient fibers, and decreased respiratory chain enzyme activities. Metabolic laboratory investigations revealed elevated blood and cerebrospinal fluid lactate. Heteroplasmy levels in affected individuals were highest in muscle and/or liver when multiple tissues were assessed (25 - >95 % in muscle, 1 to >95% in blood, >95% in liver, 1-92% in skin fibroblasts, and 5% in urine when assessed). Functional studies to support variant pathogenicity. Sources: Expert list |
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| Mendeliome v1.3223 | MT-TV |
Zornitza Stark gene: MT-TV was added gene: MT-TV was added to Mendeliome. Sources: Expert list mtDNA tags were added to gene: MT-TV. Mode of inheritance for gene gene: MT-TV was set to MITOCHONDRIAL Publications for gene: MT-TV were set to 9450773; 12056939; 19252805; 15320572; 18314141; 24691472 Phenotypes for gene: MT-TV were set to Mitochondrial disease (MONDO:0044970), MT-TV-related Review for gene: MT-TV was set to GREEN Added comment: DEFINITIVE by ClinGen. At least 8 individuals reported. Age of onset in affected individuals ranged from childhood to adulthood. Clinical features in affected individuals included LSS, cognitive decline, fatigue, migraines, seizures, myoclonic jerks, ataxia, dystonia, dysarthria, imbalance, muscle weakness, axonal sensorimotor polyneuropathy, diabetes, gastrointestinal dysmotility, cataracts, retinitis pigmentosa, sensorineural hearing loss, and hypertrophic cardiomyopathy. Brain imaging was variable and ranged from normal to findings consistent with LSS, cerebellar and cerebral atrophy, brainstem atrophy, and basal ganglia calcifications. Muscle biopsies showed ragged red fibers, COX-deficient fibers, and normal to decreased respiratory chain enzyme activities. Metabolic laboratory investigations revealed elevated lactate. Heteroplasmy levels in affected individuals were highest in muscle when multiple tissues were assessed (67% to homoplasmic in muscle, 70% to homoplasmic in blood, and homoplasmic in skin fibroblasts). Sources: Expert list |
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| Mendeliome v1.3198 | MT-TI |
Zornitza Stark gene: MT-TI was added gene: MT-TI was added to Mendeliome. Sources: Expert list mtDNA tags were added to gene: MT-TI. Mode of inheritance for gene gene: MT-TI was set to MITOCHONDRIAL Publications for gene: MT-TI were set to 15121771; 21982779; 23395828; 16120360; 9473477; 12767666; 10065021; 7646516; 20884012; 21292040; 1632786; 23696415; 34607911 Phenotypes for gene: MT-TI were set to Mitochondrial disease (MONDO:0044970), MT-TI-related Review for gene: MT-TI was set to GREEN Added comment: DEFINITIVE by ClinGen. More than 10 individuals reported. Clinical presentations included LSS, myoclonic epilepsy with ragged red fibers (MERRF) and chronic progressive external ophthalmoplegia (CPEO), in addition to rhabdomyolysis, cardiomyopathy, encephalopathy, exercise intolerance, muscle weakness, hypertension2, hypercholesterolaemia, and hypomagnesaemia. Heteroplasmy levels of MT-TI can be variable in tissues from the same individual. In general, variants tend to be lower in tissues such as blood, saliva, and buccal swab and urine and muscle heteroplasmy levels tend to be higher. Sources: Expert list |
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| Mendeliome v1.3179 | MT-ND6 |
Zornitza Stark gene: MT-ND6 was added gene: MT-ND6 was added to Mendeliome. Sources: Expert list mtDNA tags were added to gene: MT-ND6. Mode of inheritance for gene gene: MT-ND6 was set to MITOCHONDRIAL Publications for gene: MT-ND6 were set to 5576045; 20019223; 21196529; 10894222; 14684687; 17535832; 19103152; 21749722; 23813926; 25356405; 14595656; 19062322; 11133798; 30741831; 21364701; 2018041 Phenotypes for gene: MT-ND6 were set to Mitochondrial disease (MONDO:0044970), MT-ND6-related Review for gene: MT-ND6 was set to GREEN Added comment: DEFINITIVE by ClinGen. More than 20 affected individuals reported, the m.14484T>C and m.14487T>C variants are recurrent. Affected individuals present with a broad phenotypic spectrum of disease including Leber Hereditary Optic Neuropathy (LHON), mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), and LSS phenotypes, as well as migraines, tremor, multiple sclerosis, and cardiac involvement. The age of onset is also highly variable, ranging from infantile to adult. Muscle biopsies revealed isolated complex I deficiency, and complex I and III deficiencies; and complex I deficiency was also seen in fibroblasts and liver. Metabolic screening investigations showed elevated lactate and pyruvate in cerebrospinal fluid (CSF) and blood. Heteroplasmy levels in affected individuals ranged from 50% to >95% in skeletal muscle; 25% to >95% in blood, 76% to >95% in fibroblasts, and 65% to >95% in liver; and ranged in healthy family members from undetectable to 92% in blood, undetectable to 95% in urine, 14% to 95% in hair follicles, 16% to 68% in buccal, and was undetectable in muscle in healthy family members. Sources: Expert list |
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| Mendeliome v1.3177 | MT-ND5 |
Zornitza Stark gene: MT-ND5 was added gene: MT-ND5 was added to Mendeliome. Sources: Expert list mtDNA tags were added to gene: MT-ND5. Mode of inheritance for gene gene: MT-ND5 was set to MITOCHONDRIAL Publications for gene: MT-ND5 were set to 17400793; 11938446; 12624137; 18495510; 23918514; 17535832; 29506874; 23034978; 16816025; 9299505; 18977334 Phenotypes for gene: MT-ND5 were set to Mitochondrial disease (MONDO:0044970), MT-ND5-related Review for gene: MT-ND5 was set to GREEN Added comment: DEFINITIVE by ClinGen. More than 20 individuals reported. Two variants are recurrent (m.13513G>A and m.13094T>C). Affected individuals present with a broad phenotypic spectrum of disease including Leber Hereditary Optic Neuropathy (LHON); mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS); LSS; myoclonus epilepsy, ragged red fibers (MERRF); and cardiomyopathy. The age of onset is also highly variable, ranging from infantile to adult. Muscle biopsies variably revealed ragged red fibers, isolated complex I deficiency, and variable combined deficiencies of complexes I, III, and/or IV. Metabolic screening investigations showed elevated lactate in cerebrospinal fluid (CSF) and blood and urinary excretion of Krebs cycle intermediates. Heteroplasmy levels in affected individuals ranged from 28% - 90% in skeletal muscle, 23% to 77% in blood, undetectable to 90% in fibroblasts, 51% - 81% in urine; and ranged in healthy family members from undetectable to 20% in blood, undetectable to 25% to 95% in hair follicles, undetectable to 4-6% muscle, and ranged from 27%-45% in other tissues such as urine and buccal samples in healthy family members. Sources: Expert list |
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| Mendeliome v1.3173 | MT-ND4 |
Zornitza Stark gene: MT-ND4 was added gene: MT-ND4 was added to Mendeliome. Sources: Expert list mtDNA tags were added to gene: MT-ND4. Mode of inheritance for gene gene: MT-ND4 was set to MITOCHONDRIAL Publications for gene: MT-ND4 were set to 12707444; 16120329; 15576045; 20502985; 27761019; 32445240; 32659360; 3201231 Phenotypes for gene: MT-ND4 were set to Mitochondrial disease (MONDO:0044970), MT-ND4-related Review for gene: MT-ND4 was set to GREEN Added comment: DEFINITIVE by ClinGen. Multiple individuals reported presenting with a broad phenotypic spectrum of clinical features including Leber Hereditary Optic Neuropathy (LHON); mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS); LSS; cerebellar ataxia, migraines, regression, developmental delay, leukoencephalopathy, myoclonus, seizures, stroke-like episodes, cognitive decline, psychiatric illness, Parkinsonism, axonal neuropathy, multiple sclerosis, ophthalmoplegia, short stature, and hypertrophic cardiomyopathy. Age of onset varied from infancy to adulthood. Muscle biopsy showed COX-negative fibers and complex I deficiency. Heteroplasmy levels in affected individuals ranged from 60% - 83% in muscle, 40% - 80% in blood, and 76% - 78% in myoblasts, as well as from 57% - 73% in various other tissues (fibroblasts, liver, urine, buccal). Of note, the m.11778G>A common LHON variant was reported in affected individuals in the homoplasmic and heteroplasmic states. Sources: Expert list |
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| Mendeliome v1.3171 | MT-ND3 |
Zornitza Stark gene: MT-ND3 was added gene: MT-ND3 was added to Mendeliome. Sources: Expert list mtDNA tags were added to gene: MT-ND3. Mode of inheritance for gene gene: MT-ND3 was set to MITOCHONDRIAL Publications for gene: MT-ND3 were set to 1928099; 14705112; 14764913; 17152068; 20202874; 25118196; 25384404; 11456298; 19458970; 30199507; 29237403 Phenotypes for gene: MT-ND3 were set to Mitochondrial disease (MONDO:0044970), MT-ND3-related Review for gene: MT-ND3 was set to GREEN Added comment: DEFINITIVE by ClinGen. More than 15 affected individuals reported. Three variants are recurrent (m.10158T>C, m.10191T>C, m.10197G>A). Affected individuals present with a broad phenotypic spectrum of clinical features including LSS; Leber Hereditary Optic Neuropathy (LHON); mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS); lactic acidosis, epilepsia partialis continua (EPC), epileptic encephalopathy, dystonia, and optic atrophy. The age of onset is also highly variable, ranging from infantile to adult. Muscle biopsy showed and complex I deficiency. Sources: Expert list |
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| Mendeliome v0.286 | LSS | Zornitza Stark Marked gene: LSS as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.286 | LSS | Zornitza Stark Gene: lss has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.286 | LSS | Zornitza Stark Classified gene: LSS as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.286 | LSS | Zornitza Stark Gene: lss has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.285 | LSS |
Zornitza Stark gene: LSS was added gene: LSS was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: LSS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LSS were set to 30723320 Phenotypes for gene: LSS were set to Cataract 44, OMIM #616509; Hypotrichosis 14, OMIM #618275; Intellectual disability Review for gene: LSS was set to GREEN Added comment: Expanded the phenotypic spectrum of LSS to a recessive neuroectodermal syndrome formerly named alopecia with mental retardation (APMR) syndrome. Ten APMR individuals from 6 unrelated families with biallelic variants in LSS. Quantification of cholesterol and its precursors did not reveal noticeable imbalance. Sources: Literature |
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